BACKGROUND: Intrauterine growth restriction (IUGR) is associated with cardiovascular remodeling persisting into adulthood. Mitochondrial bioenergetics, essential for embryonic development and cardiovascular function, are regulated by nuclear effectors as sirtuins. A rabbit model of IUGR and cardiovascular remodeling was generated, in which heart mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the etiopathology and potential therapeutic targets for this obstetric complication...

Alzheimer's disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons...

Persistent mitochondrial injury occurs after acute kidney injury (AKI) and mitochondria-targeted antioxidant Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (MT) has shown benefits for AKI, but its efficiency is limited by short half-life and side effect in vivo. Self-assembling peptide (SAP) hydrogel is a robust platform for drug delivery. This study aims to develop an SAP-based carrier to slow release MT for enhancing its long-term therapeutic potency on AKI. The KLD with aspartic acid (KLDD) was designed...

PURPOSE: Improving the targeting efficiency of imaging agents or anticancer drugs has become essential in the current primary mission to enhance the diagnostic or therapeutic effects. To improve the tumor diagnosis and therapy effect, a promising drug-delivery and targeting strategy was established based on the bioorthogonal chemistry. METHOD: The delivery system was composed of the pre-targeting carrier Biotin-MSNs-DBCO nanoparticles and the azido cargoes. The fluorescence probe 1-(3-azidopropyl) fluorescein (FITC-N 3 ) and ruthenium N-heterocyclic carbene complex N 3 -S-S-NHC-Ru were synthesized and served as the tumor imaging and therapy probes, respectively...

Background: Cancer is one of the major heterogeneous disease with high morbidity and mortality with poor prognosis. Elevated levels of reactive oxygen species (ROS), alteration in redox balance, and deregulated redox signaling are common hallmarks of cancer progression and resistance to treatment. Mitochondria contribute mainly in the generation of ROS during oxidative phosphorylation. Elevated levels of ROS have been detected in cancers cells due to high metabolic activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction, activation of oncogene, and increased enzymatic activity of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylases...

Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...

Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia than in the general population, and these metabolic abnormalities are further aggravated by second generation antipsychotic (SGA) drugs. Although the underlying mechanisms responsible for the increased prevalence of MetS among patients under SGA treatment are not well understood, alterations in mitochondria function have been implicated. We performed a comprehensive evaluation of the role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in schizophrenia...

Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA)...

BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay...

Mitochondrial dysfunction caused by cigarette smoke is involved in the oxidative stress-induced pathology of airway diseases. Reducing the levels of harmful and potentially harmful constituents by heating rather than combusting tobacco may reduce mitochondrial changes that contribute to oxidative stress and cell damage. We evaluated mitochondrial function and oxidative stress in BEAS-2B human bronchial epithelial cells following 1- and 12-week exposures to total particulate matter (TPM) from the aerosol of a candidate modified-risk tobacco product, the Tobacco Heating System 2...

The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia and sedation in critical patient care. However, the rare but severe complication propofol infusion syndrome (PRIS) can occur, especially in patients receiving high doses of propofol for prolonged periods. In vivo and in vitro evidence suggests that the propofol toxicity is related to the impaired mitochondrial function. However, underlying molecular mechanisms remain unknown. Therefore, we investigated effects of propofol on cell metabolism and death using a series of established cell lines of various origins, including neurons, myocytes, and trans-mitochondrial cybrids, with defined mitochondrial DNA deficits...

BACKGROUND: Excessive norepinephrine (NE) release in the ischemic heart elicits severe and often lethal arrhythmias. Resident cardiac mast cells synthesize and store active renin, which is released upon degranulation, causing the activation of a local cardiac renin-angiotensin system (RAS) responsible for NE release and consequent arrhythmias. Toxic aldehydes, known to be formed by lipid peroxidation in ischemia/reperfusion (I/R), have been shown to degranulate mast cells and activate a local RAS...

Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism...

Neurological and psychiatric disorders are leading contributors to the global disease burden, having a serious impact on the quality of life of both patients and their relatives. Although the molecular events underlying these heterogeneous diseases remain poorly understood, some studies have raised the idea of common mechanisms involved. In excitotoxicity, there is an excessive activation of glutamate receptors by excitatory amino acids, leading to neuronal damage. Thus, the excessive release of glutamate can lead to a dysregulation of Ca 2+ homeostasis, triggering the production of free radicals and oxidative stress, mitochondrial dysfunction and eventually cell death...

BACKGROUND: Monogenic defects of synaptic vesicle (SV) homeostasis have been implicated in many neurologic diseases, including autism, epilepsy, and movement disorders. In addition, abnormal vesicle exocytosis has been associated with several endocrine dysfunctions. METHODS: We report an 11 year old girl with learning disabilities, tremors, ataxia, transient hyperglycemia, and muscle fatigability responsive to albuterol sulfate. Failure of neuromuscular transmission was confirmed by single fiber electromyography...

A high level of circulating free fatty acids (FFAs) is known to be an important trigger for macrophage apoptosis during the development of atherosclerosis. However, the underlying mechanism by which FFAs result in macrophage apoptosis is not well understood. In cultured human macrophage Thp-1 cells, we showed that palmitate (PA), the most abundant FFA in circulation, induced excessive reactive oxidative substance production, increased malondialdehyde concentration, and decreased adenosine triphosphate levels...

Repair and removal of damaged mitochondria is a key process for eukaryotic cell homeostasis. Here we investigate in the yeast model how different protein complexes of the mitochondrial electron transport chain are subject to specific degradation upon high respiration load and organelle damage. We find that the turnover of subunits of the electron transport complex I equivalent and complex III is preferentially stimulated upon high respiration rates. Particular mitochondrial proteases, but not mitophagy, are involved in this activated degradation...

Dynamic feedback based closed-loop medical devices offer a number of advantages for treatment of heterogeneous neurological conditions. Closed-loop devices integrate a level of neurobiological feedback, which allows for real-time adjustments to be made with the overarching aim of improving treatment efficacy and minimizing risks for adverse events. One target which has not been extensively explored as a potential feedback component in closed-loop therapies is mitochondrial function. Several neurodegenerative and psychiatric disorders including Parkinson's disease, Major Depressive disorder and Bipolar disorder have been linked to perturbations in the mitochondrial respiratory chain...

Long-term outcomes of perinatal exposure to maternal antiretroviral therapy in HIV-exposed uninfected (HEU) children are unknown. However, both HIV antiretroviral therapy and autism spectrum disorder (ASD) have been associated with mitochondrial alterations. Leukocyte mitochondrial DNA (mtDNA) content can serve as a marker for mitochondrial dysfunction. In this cross-sectional, nested case-control study, HEU children with ASD were matched approximately 1:3 on age, sex, and ethnicity to HEU children without ASD, HIV-unexposed uninfected (HUU) controls, and HUU children with ASD...

Reactive oxygen species (ROS) are formed in mitochondria during electron transport and energy generation. Elevated levels of ROS lead to increased amounts of mitochondrial DNA (mtDNA) damage. We report that levels of M1dG, a major endogenous peroxidation-derived DNA adduct, are 50-100-fold higher in mtDNA than in nuclear DNA in several different human cell lines. Treatment of cells with agents that either increase or decrease mitochondrial superoxide levels leads to increased or decreased levels of M1dG in mtDNA, respectively...